1. Field of the Invention
This invention relates to a process for producing plasminogen activator in high yields utilizing animal cells.
2. Description of the Prior Art
Isolation and purification from human urine has previously been well known as a commercial process for producing plasminogen activator as described in W. F. White, Biochemistry, 5 2160, 1966. This conventional process, however, has the defect that the quality of human urine as a raw material is not uniform, the handling of urine poses a hygienic problem, and it is difficult to collect large quantities of urine from healthy persons.
Animal cells are known to provide plasminogen activator, as reported by Bernik et al in J. Lab. & Clin. Med., 70 650 (1967). The Bernik procedure is not satisfactory for producing plasminogen activator on an industrial scale due to its low yields. However, it was believed that if yields could be improved the process of using animal cells to produce plasminogen activator could be adapted to an industrial scale and it would be possible to supply large quantities of raw material of uniform quality without the risk of contamination. Thus we desired to establish a technique which would render the use of animal cells commercially acceptable.
Extensive investigations have been directed to a process for producing plasminogen activator using animal cells. These investigations have led to the discovery that when an organic acid selected from fumaric acid, malic acid, succinic acid and glycolic acid is present in the aqueous nutrient solution with which animal cells are contacted to produce plasminogen activator, the amount of activator increases strikingly.